Method for treating tissue with an implant

ABSTRACT

A method for forming a valve-like mechanism in a body of a mammal having an esophagus extending through a lower esophageal sphincter to a stomach and formed by a wall having a muscle layer and a mucosal layer. The method comprises the step of forming at least one implant in the muscle layer of the wall in the vicinity of the lower esophageal sphincter. The at least one implant inhibits opening of esophagus at the lower esophageal sphincter and causes the mucosal layer to appose in the vicinity of the implants.

This application is a continuation application of U.S. utility patentapplication Ser. No. 10/455,683 filed Jun. 4, 2003, now U.S. Pat. No.7,056,277, which is a continuation application of U.S. utility patentapplication Ser. No. 09/852,403 filed May 9, 2001, now U.S. Pat. No.6,595,909, which is a continuation application of U.S. patentapplication Ser. No. 09/447,663 filed Nov. 23, 1999, now U.S. Pat. No.6,251,046, which claims the benefit of U.S. provisional patentapplication Ser. No. 60/149,569 filed Aug. 18, 1999 and is acontinuation-in-part of U.S. patent application Ser. No. 09/286,245filed Apr. 5, 1999, now U.S. Pat. No. 6,251,063, which is acontinuation-in-part of U.S. patent application Ser. No. 09/232,056filed Jan. 15, 1999, now U.S. Pat. No. 6,238,335, and claims the benefitof U.S. provisional patent application Ser. No. 60/111,884 filed Dec.11, 1998, the entire contents of which are incorporated herein by thisreference.

This invention pertains to the treatment of the gastrointestinal tract,and more particularly, to the formation of implants in the wall formingthe gastrointestinal tract.

U.S. Pat. No. 6,251,063 describes a method and device for augmenting orbulking gastrointestinal tract walls by injecting at least onenonaqueous material into the walls in order to form one or morenonbiodegradable solid implants therein. There is a need for a methodfor more predictably forming and placing implants in gastrointestinaltract walls which are more clinically efficacious.

In general, it is an object of the present invention to provide a methodfor creating a valve-like mechanism in a natural body passageway.

Another object of the invention is to provide a method of the abovecharacter in which at least one implant is formed in the wall formingthe natural body passageway.

Another object of the invention is to provide a method of the abovecharacter in which a plurality of circumferentially disposed implantsare formed in the wall forming the natural body passageway.

Another object of the invention is to provide a method of the abovecharacter in which an arcuate implant extending circumferentially aroundat least a portion of the natural body passageway is formed.

Another object of the invention is to provide a method of the abovecharacter in which a ring-like implant is formed in the wall forming thenatural body passageway.

Another object of the invention is to provide a method of the abovecharacter for enhancing the lower esophageal sphincter.

Additional objects and features of the invention will appear from thefollowing description from which the preferred embodiments are set forthin detail in conjunction with the accompanying drawings.

FIG. 1 is a schematic view with the device in place in the stomach andlower esophagus for treatment by the method of the present invention.

FIG. 2 is a cross-sectional view of the lower portion of the esophagusand a portion of the stomach with the device in place and an implantformed by the method of the present invention.

FIG. 3 is a frontal view partially in section of the lower esophagus anda non-distended stomach with implants as treated by the method of thepresent invention.

FIG. 4 is a cross-sectional view taken along the line 4-4 of FIG. 3.

FIG. 5 is a frontal view partially in section of the lower esophagus anddistended stomach with implants treated by the method of the presentinvention.

FIG. 6 is a schematic view of a cross section of the lower esophagus andnon-distended stomach with implants demonstrating esophageal mucosal andesophageal muscle layers in register with one another.

FIG. 7 is a schematic view similar to FIG. 6 in which the stomach isdistended and wherein the implants are functioning as a valve-likemechanism.

FIG. 8 is a cross-sectional view, similar to FIG. 4, of the wall formingthe lower portion of the esophagus with a plurality of arcuate implantsformed therein.

FIG. 9 is a cross-sectional view, similar to FIG. 8, of the wall formingthe lower portion of the esophagus with a ring-like implant formedtherein.

In general, a method for forming a valve-like mechanism in a body of amammal having an esophagus extending through a lower esophagealsphincter to a stomach and formed by a wall having a muscle layer and amucosal layer is provided. At least one implant is formed in the musclelayer of the wall in the vicinity of the lower esophageal sphincter. Theimplant inhibits opening of the esophagus at the lower esophagealsphincter and causes the mucosal layer to appose in the vicinity of theimplants.

The method of the present invention is for use in a natural body cavitysuch as the gastrointestinal tract in a body of a mammal. A portion of ahuman body 21 is shown in FIG. 1 and has an internal cavity in the formof the passage of the esophagus 22 extending through a lower esophagealsphincter 23 to a stomach 24. Such cavity is accessible by a naturalbody opening in the form of mouth 26 and is defined by wall 27.Esophagus 22 is part of the gastrointestinal tract of body 21 thatextends from mouth 26 to an anus (not shown).

Esophageal mucosa 28 serves as the inner layer of the intraluminal wall27 in esophagus 22 and the gastric mucosa 29 serves as the inner layerof the intramural wall 27 in stomach 24. Esophageal mucosa 28 andgastric mucosa 29 meet at the squamous columnar junction 31. Wall 27 hasa muscle layer comprising layer of circular muscle 32 extending beneathmucosa layers 28 and 29 and layer of longitudinal muscle 33 beneathcircular muscle 32. Muscle layers 32 and 33 each extend around esophagus22 and stomach 24. Wall 27 further includes a submucosal layer orsubmucosa 34 extending between the mucosa and the muscle layers. Asubmucosal space, that is a potential space, can be created betweenmucosal layer 28 or 29 and circular muscle layer 32 by the separation oflayer 28 or 29 from muscle layer 32. In addition, as with any muscle,wall 27 includes an intramuscular potential space, that is a space whichcan be created intramuscularly by distension and separation of musclefibers within a single muscle. Wall 27 has a depth or thickness whichincludes at least mucosal layers 28 and 29, muscle layers 32 and 33 andthe submucosal layer 34. The phreno-esophageal ligament 36 and diaphragm37 extend around esophagus 22 above the lower esophageal sphincter 23.

The method of the present invention can be performed with any of theapparatus disclosed in U.S. Pat. Nos. 6,251,063 and 6,238,335. Ingeneral, a suitable apparatus or medical device 41 includes a probemember or probe 42 having an optical viewing device. A conventional orother suitable gastroscope or endoscope can be used for probe 42. Anexemplary probe is an Olympus CF Type 40L/I endoscope made by OlympusCorporation of Tokyo, Japan. A needle assembly 43 is slidably carried byprobe 42. Needle assembly 43 can be of any conventional type, such as amodified sclerotherapy needle similar to the Bard® Flexitip™ needlemanufactured by C.R. Bard, Inc. of Billerica, Md., and includes a needlemember or needle 44 and protective sleeve 46. Device 41 further includesa supply assembly (not shown) mounted to the proximal end portion ofneedle assembly 43. The supply assembly is secured to the proximalextremity of needle assembly 43 and can include a conventional syringefor introducing a liquid or solution through needle 44. The supplyassembly optionally includes second and third reservoirs in the form ofsecond and third syringes. The second syringe is filled with dimethylsulfoxide (DMSO) or any other suitable liquid. The third syringe isfilled with a saline solution or any other suitable aqueous orphysiological solution.

In the method of the present invention, at least one implant forming,solution is introduced into the wall 27 of the gastrointestinal tract toform at least one implant in the wall 27 of the gastrointestinal tract.Any suitable material, from which an implant can be formed when thefluid, separately or in conjunction with another fluid, is introducedinto the body can be used with the method of the present invention.Although aqueous or non-aqueous solutions are amongst the fluids thatcan be used, an inert, nonresorbable material is preferred. One suchmaterial comprises at least one solution which when introduced into thebody forms a nonbiodegradable solid. As used herein, a solid means anysubstance that does not flow perceptibly under moderate stress, has adefinite capacity for resisting forces which tend to deform it (such ascompression, tension and strain) and under ordinary conditions retains adefinite size and shape; such a solid includes, without limitation,spongy and/or porous substances. One such embodiment of the at least onesolution is first and second solutions which when combined in the bodyform the nonbiodegradable solid. Another such embodiment is a nonaqueoussolution which can be introduced into the body as a liquid and fromwhich a solid thereafter precipitates. A preferred embodiment of such anonaqueous solution is a solution of a biocompatible polymer and abiocompatible solvent which can optionally include a contrast agent forfacilitating visualization of the solution in the body.

A particularly preferred implant forming solution is a compositioncomprising from about 2.5 to about 8.0 weight percent of a biocompatiblepolymer, from about 52 to about 87.5 weight percent of a biocompatiblesolvent and optionally from about 10 to about 40 weight percent of abiocompatible contrast agent having a preferred average particle size ofabout 10 μm or less. It should be appreciated that any percents statedherein which include a contrast agent would be proportionally adjustedwhen the contrast agent is not utilized. Any contrast agent ispreferably a water insoluble biocompatible contrast agent. The weightpercent of the polymer, contrast agent and biocompatible solvent isbased on the total weight of the complete composition. In a preferredembodiment, the water insoluble, biocompatible contrast agent isselected from the group consisting of barium sulfate, tantalum powderand tantalum oxide. In still a further preferred embodiment, thebiocompatible solvent is dimethylsulfoxide (DMSO), ethanol, ethyllactate or acetone.

The term “biocompatible polymer” refers to polymers which, in theamounts employed, are non-toxic, chemically inert, and substantiallynon-immunogenic when used internally in the patient and which aresubstantially insoluble in physiologic liquids. Suitable biocompatiblepolymers include, by way of example, cellulose acetates (includingcellulose diacetate), ethylene vinyl alcohol copolymers, hydrogels(e.g., acrylics), poly(C₁-C₆) acrylates, acrylate copolymers, polyalkylalkacrylates wherein the alkyl and alk groups independently contain oneto six carbon atoms, polyacrylonitrile, polyvinylacetate, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid, and mixtures thereof. Copolymers ofurethane/carbonate include polycarbonates that are diol terminated whichare then reacted with a diisocyanate such as methylene bisphenyldiisocyanate to provide for the urethane/carbonate copolymers. Likewise,copolymers of styrene/maleic acid refer to copolymers having a ratio ofstyrene to maleic acid of from about 7:3 to about 3:7. Preferably, thebiocompatible polymer is also non-inflammatory when employed in situ.The particular biocompatible polymer employed is not critical and isselected relative to the viscosity of the resulting polymer solution,the solubility of the biocompatible polymer in the biocompatiblesolvent, and the like. Such factors are well within the skill of theart.

The polymers of polyacrylonitrile, polyvinylacetate, poly(C₁-C₆)acrylates, acrylate copolymers, polyalkyl alkacrylates wherein the alkyland alk groups independently contain one to six carbon atoms, celluloseacetate butyrate, nitrocellulose, copolymers of urethane/carbonate,copolymers of styrene/maleic acid and mixtures thereof typically willhave a molecular weight of at least about 50,000 and more preferablyfrom about 75,000 to about 300,000.

Preferred biocompatible polymers include cellulose diacetate andethylene vinyl alcohol copolymer. In one embodiment, the cellulosediacetate has an acetyl content of from about 31 to about 40 weightpercent. Cellulose diacetate polymers are either commercially availableor can be prepared by art recognized procedures. In a preferredembodiment, the number average molecular weight, as determined by gelpermeation chromatography, of the cellulose diacetate composition isfrom about 25,000 to about 100,000 more preferably from about 50,000 toabout 75,000 and still more preferably from about 58,000 to 64,000. Theweight average molecular weight of the cellulose diacetate composition,as determined by gel permeation chromatography, is preferably from about50,000 to 200,000 and more preferably from about 100,000 to about180,000. As is apparent to one skilled in the art, with all otherfactors being equal, cellulose diacetate polymers having a lowermolecular weight will impart a lower viscosity to the composition ascompared to higher molecular weight polymers. Accordingly, adjustment ofthe viscosity of the composition can be readily achieved by mereadjustment of the molecular weight of the polymer composition.

Ethylene vinyl alcohol copolymers comprise residues of both ethylene andvinyl alcohol monomers. Small amounts (e.g., less than 5 mole percent)of additional monomers can be included in the polymer structure orgrafted thereon provided such additional monomers do not alter theimplanting properties of the composition. Such additional monomersinclude, by way of example only, maleic anhydride, styrene, propylene,acrylic acid, vinyl acetate and the like.

Ethylene vinyl alcohol copolymers are either commercially available orcan be prepared by art recognized procedures. Preferably, the ethylenevinyl alcohol copolymer composition is selected such that a solution of8 weight-volume percent of the ethylene vinyl alcohol copolymer in DMSOhas a viscosity equal to or less than 60 centipoise at 20° C. and morepreferably 40 centipoise or less at 20° C. As is apparent to one skilledin the art, with all other factors being equal, copolymers having alower molecular weight will impart a lower viscosity to the compositionas compared to higher molecular weight copolymers. Accordingly,adjustment of the viscosity of the composition as necessary for catheterdelivery can be readily achieved by mere adjustment of the molecularweight of the copolymer composition.

As is also apparent, the ratio of ethylene to vinyl alcohol in thecopolymer affects the overall hydrophobicity/hydrophilicity of thecomposition which, in turn, affects the relative watersolubility/insolubility of the composition as well as the rate ofprecipitation of the copolymer in an aqueous solution. In a particularlypreferred embodiment, the copolymers employed herein comprise a molepercent of ethylene of from about 25 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 75, more preferably a molepercent of ethylene of from about 40 to about 60 and a mole percent ofvinyl alcohol of from about 40 to about 60.

The term “contrast agent” refers to a biocompatible (non-toxic)radiopaque material capable of being monitored during injection into amammalian subject by, for example, radiography. The contrast agent canbe either water soluble or water insoluble. Examples of water solublecontrast agents include metrizamide, iopamidol, iothalamate sodium,iodomide sodium, and meglumine. The term “water insoluble contrastagent” refers to contrast agents which are insoluble in water (i.e., hasa water solubility of less than 0.01 milligrams per milliliter at 20°C.) and include tantalum, tantalum oxide and barium sulfate, each ofwhich is commercially available in the proper form for in vivo use andpreferably having a particle size of 10 μm or less. Other waterinsoluble contrast agents include gold, tungsten and platinum powders.Methods for preparing such water insoluble biocompatible contrast agentshaving an average particle size of about 10 μm or less are describedbelow. Preferably, the contrast agent is water insoluble (i.e., has awater solubility of less than 0.01 mg/ml at 20° C.)

The term “biocompatible solvent” refers to an organic material liquid atleast at body temperature of the mammal in which the biocompatiblepolymer is soluble and, in the amounts used, is substantially non-toxic.Suitable biocompatible solvents include, by way of example,dimethylsulfoxide, analogues/homologues of dimethylsulfoxide, ethanol,ethyl lactate, acetone, and the like. Aqueous mixtures with thebiocompatible solvent can also be employed provided that the amount ofwater employed is sufficiently small that the dissolved polymerprecipitates upon injection into a human body. Preferably, thebiocompatible solvent is ethyl lactate or dimethylsulfoxide.

The compositions employed in the methods of this invention are preparedby conventional methods whereby each of the components is added and theresulting composition mixed together until the overall composition issubstantially homogeneous. For example, sufficient amounts of theselected polymer are added to the biocompatible solvent to achieve theeffective concentration for the complete composition. Preferably, thecomposition will comprise from about 2.5 to about 8.0 weight percent ofthe polymer based on the total weight of the composition and morepreferably from about 4 to about 5.2 weight percent. If necessary,gentle heating and stirring can be used to effect dissolution of thepolymer into the biocompatible solvent, e.g., 12 hours at 50° C.

Sufficient amounts of the contrast agent are then optionally added tothe biocompatible solvent to achieve the effective concentration for thecomplete composition. Preferably, the composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 to about 35 weight percent. When the contrast agentis not soluble in the biocompatible solvent, stirring is employed toeffect homogeneity of the resulting suspension. In order to enhanceformation of the suspension, the particle size of the contrast agent ispreferably maintained at about 10 μm or less and more preferably at fromabout 1 to about 5 μm (e.g., an average size of about 2 μm). In onepreferred embodiment, the appropriate particle size of the contrastagent is prepared, for example, by fractionation. In such an embodiment,a water insoluble contrast agent such as tantalum having an averageparticle size of less than about 20 microns is added to an organicliquid such as ethanol (absolute) preferably in a clean environment.Agitation of the resulting suspension followed by settling forapproximately 40 seconds permits the larger particles to settle faster.Removal of the upper portion of the organic liquid followed byseparation of the liquid from the particles results in a reduction ofthe particle size which is confirmed under an optical microscope. Theprocess is optionally repeated until a desired average particle size isreached.

The particular order of addition of components to the biocompatiblesolvent is not critical and stirring of the resulting suspension isconducted as necessary to achieve homogeneity of the composition.Preferably, mixing/stirring of the composition is conducted under ananhydrous atmosphere at ambient pressure. The resulting composition isheat sterilized and then stored preferably in sealed amber bottles orvials until needed.

Each of the polymers recited herein is commercially available but canalso be prepared by methods well known in the art. For example, polymersare typically prepared by conventional techniques such as radical,thermal, UV, gamma irradiation, or electron beam induced polymerizationemploying, as necessary, a polymerization catalyst or polymerizationinitiator to provide for the polymer composition. The specific manner ofpolymerization is not critical and the polymerization techniquesemployed do not form a part of this invention. In order to maintainsolubility in the biocompatible solvent, the polymers described hereinare preferably not cross-linked.

In another particularly preferred embodiment of the nonaqueous solution,the biocompatible polymer composition can be replaced with abiocompatible prepolymer composition containing a biocompatibleprepolymer. In this embodiment, the composition comprises abiocompatible prepolymer, an optional biocompatible water insolublecontrast agent preferably having an average particle size of about 10 μmor less and, optionally, a biocompatible solvent.

The term “biocompatible prepolymer” refers to materials which polymerizein situ to form a polymer and which, in the amounts employed, arenon-toxic, chemically inert, and substantially non-immunogenic when usedinternally in the patient and which are substantially insoluble inphysiologic liquids. Such a composition is introduced into the body as amixture of reactive chemicals and thereafter forms a biocompatiblepolymer within the body. Suitable biocompatible prepolymers include, byway of example, cyanoacrylates, hydroxyethyl methacrylate, siliconprepolymers, and the like. The prepolymer can either be a monomer or areactive oligomer. Preferably, the biocompatible prepolymer is alsonon-inflammatory when employed in situ.

Prepolymer compositions can be prepared by adding sufficient amounts ofthe optional contrast agent to the solution (e.g., liquid prepolymer) toachieve the effective concentration for the complete polymercomposition. Preferably, the prepolymer composition will comprise fromabout 10 to about 40 weight percent of the contrast agent and morepreferably from about 20 to about 40 weight percent and even morepreferably about 30 weight percent. When the contrast agent is notsoluble in the biocompatible prepolymer composition, stirring isemployed to effect homogeneity of the resulting suspension. In order toenhance formation of the suspension, the particle size of the contrastagent is preferably maintained at about 10 μm or less and morepreferably at from about 1 to about 5 μm (e.g., an average size of about2 μm).

When the prepolymer is liquid (as in the case of polyurethanes), the useof a biocompatible solvent is not absolutely necessary but may bepreferred to provide for an appropriate viscosity in the nonaqueoussolution. Preferably, when employed, the biocompatible solvent willcomprise from about 10 to about 50 weight percent of the biocompatibleprepolymer composition based on the total weight of the prepolymercomposition. When a biocompatible solvent is employed, the prepolymericcomposition typically comprises from about 90 to about 50 weight percentof the prepolymer based on the total weight of the composition.

In a particularly preferred embodiment, the prepolymer is cyanoacrylatewhich is preferably employed in the absence of a biocompatible solvent.When so employed, the cyanoacrylate adhesive is selected to have aviscosity of from about 5 to about 20 centipoise at 20° C.

The particular order of addition of components is not critical andstirring of the resulting suspension is conducted as necessary toachieve homogeneity of the composition. Preferably, mixing/stirring ofthe composition is conducted under an anhydrous atmosphere at ambientpressure. The resulting composition is sterilized and then storedpreferably in sealed amber bottles or vials until needed.

Specific embodiments of nonaqueous solutions suitable for use in theapparatus and methods of the invention are described in U.S. Pat. No.5,667,767 dated Sep. 16, 1997, U.S. Pat. No. 5,580,568 dated Dec. 3,1996 and U.S. Pat. No. 5,695,480 dated Dec. 9, 1997 and InternationalPublication Number WO 97/45131 having an International Publication Dateof Dec. 4, 1997, the entire contents of which are incorporated herein bythis reference.

Use of the method of the present invention to create a valve-likemechanism in a human esophagus may be described as follows. Let it beassumed that in preparing for the valve-like forming procedure, thegastrointestinal tract of a patient has previously been evaluated byusing any or all techniques and procedures available in the artincluding, but not limited to, upper gastrointestinal radiographicstudies, esophageal endoscopy with biopsies and esophageal motilitystudies. Assuming that the patient's pretreatment evaluation diagnosesgastro-esophageal reflux which warrants the procedure hereinafterdescribed, the patient can be brought into an outpatient clinic or anoperating room in a hospital. The patient is preferably placed in asemi-recumbent or lateral decubitus position on an operating orexamining table or on a gurney.

After intravenous access has been accomplished and the patient has beenappropriately sedated or anesthetized, the distal extremity of probe 42is introduced through mouth 26 of the patient into esophagus 22. In thisregard, the handle of probe 42 is grasped by the physician to introducethe distal extremity of probe 42 into mouth 26 and advance it downesophagus 22 to the vicinity of the area to be treated. The opticalviewing device facilities advancement by the physician of probe 42.

The distal end portion of needle assembly 43 is introduced through probe42 and advanced until the distal end portions of needle 44 and sleeve 46are in the vicinity of the distal extremity of probe 42. Under theguidance of the optical viewing device, the distal extremity of theprobe 42 is maneuvered to a position above the portion of wall 27 whichis to be treated. In a preferred method, the distal extremity of probe42 is positioned in the vicinity of lower esophageal sphincter 23. Thephysician retracts sleeve 46 relative to needle 44 so that the distalend portion of needle 44 extends beyond the distal end portion of sleeve46 a desired amount. The physician primes needle 44 with the saline orother aqueous or physiologic solution.

After the physician penetrates wall 27 with the sharpened end of needle44, in one of the methods of the invention a saline solution can beinjected into wall 27 and more specifically into one of muscle layers 32or 33 or between the layers 32 and 33. The saline injection creates anenlargement in wall 27 having an internal space filled with the salinesolution. The amount of injected saline solution can range from 0.25 to10 cc and preferably ranges from 1 to 3 cc.

After creation of the saline-filled enlargement, the physician retractsneedle 44 from wall 27, withdraws the remaining saline solution from theneedle passage and cleanses the needle passage with DMSO to ensure thatthe saline solution has been removed from the passage. Removal of thesaline solution from the needle passage and the cleansing of the passagewith DMSO inhibits premature precipitation within syringe of thebiocompatible polymer in the implant forming solution from the DMSO inthe implant forming solution. The needle passage is next primed with theimplanting forming solution.

The physician causes the distal end portion of needle 44 to penetratethe enlargements and extend into the saline filled space therein.Thereafter, the physician causes a preselected amount of the implantforming solution to be introduced through needle 44. The optionalcontrast agent within the implanting forming solution permits theviewing of the solution by means of fluoroscopy. In addition, theintroduction of the implant forming solution into wall 27 can bemonitored by transabdominal or transesophageal ultrasound. The rate ofinjection of the implant forming solution into the space can range from0.1 cc per minute to 10 cc per minute.

Once the implant forming solution has been introduced into wall 27, thebiocompatible polymer of the implant forming solution precipitates toform one or more discrete deposits or solid implants 52 (see FIGS. 2 and4). The amount of implant forming solution injected into wall 27 foreach implant 52 can range from 0.05 cc to 10 cc. The ratio of implantforming solution to saline in the space can range from 2:1 to 1:8 andpreferably ranges from approximately one part implant forming solutionto two to three parts saline solution. In one embodiment, the spacecreated by the saline solution predefines the configuration of theprecipitant or implant 52. The discrete implant 52 can occupy less thanall of the space or, alternatively, more implant forming solution thansaline can be introduced into wall 27 so that the discrete implant 52more than fills the space created by the saline. After completion of theinjection of implant forming solution and the solidification of thebiocompatible polymer, the remaining solution within the space disperseswithin body 21 and the space contracts about implant 52.

A plurality of implants 52 are preferentially created in wall 27 in themethod of the invention. The number and configuration of implants 52formed in wall 27 can vary. In one preferred method of the invention, aplurality of implants 52 are created in wall 27 in the vicinity of thelower esophageal sphincter 23. The implants 52 are each somewhatpillow-like in shape and are preferably circumferentially spaced-apartor disposed around the periphery of the esophagus. More specifically,implants 52 are disposed substantially in a plane extendingperpendicularly to a longitudinal axis extending along the centerline ofesophagus 22. An exemplary rosette of four implants 52 spaced-apartaround the center of the rosette at approximately 90° intervals is shownin FIG. 4. It should be appreciated, however, that less than four orgreater than four implants 52 can be provided and formed in wall 27 andcan be circumferentially spaced-apart at approximately equal angularintervals or asymmetrically disposed about the center line of esophagus22. Implants 52 which merge with adjacent implants 52 in wall 27 arewithin the scope of the present invention.

The implantation of non-degradable or other materials in the esophagealsphincter 23 can form a structure which functions as an enhanced valveby at least two mechanisms occurring individually or concurrently.First, implants 52 formed and placed in appropriate positions withinlower esophagus 22 at the level or in the vicinity of lower esophagealsphincter 23, preferably within either muscle layer 32 or 33, reduce thedistensibility of esophageal sphincter 23. In FIGS. 3 and 6, stomach 24is shown after placement of two or more implants 52 and preferably aplurality of circumferentially disposed implants in muscular layer 32 sshown in FIG. 4. Expansion of stomach 24 causes esophagus 22 to shortenas hereinbefore discussed with the result that the space between implant52 and the cardia of stomach 24, identified by the reference S in FIG.6, also begins to shorten. As stomach 24 distends further space S isfurther reduced as seen in FIGS. 5 and 7.

Distension of stomach 24 causes flexible mucosal layer 28 of esophagus22 to move longitudinally or stretch and slide into stomach 24 relativeto outer muscular layers 32 and 33 of esophagus 22. An analogy can bemade to pulling the lining of a coat sleeve inside out relative to theouter shell of the coat arm. The result is that esophageal mucosalsurface 28 moves downwardly towards stomach 24 more than esophagealmuscular layers 32 and 33 as can be seen by comparing FIGS. 6 and 7. InFIG. 6, reference points 1′, 2′, 3′ and 4′ of mucosa 28 andcorresponding reference points 1, 2, 3 and 4 of muscular layers 32 and33 are respectively aligned or in register with one another. Withgreater distention as illustrated in FIG. 7, reference points 1′, 2′, 3′and 4′ have moved downwardly relative to, and are out of register with,the corresponding reference points 1, 2, 3 and 4. This downwardtranslation is also represented by arrows leading from the referencepoint 1 to the reference point 1′.

The downward movement of mucosa 28 relative to muscular layers 32 and 33results in a two-fold effect. One, the esophageal mucosa 28 is furtherand more tightly apposed in the vicinity of lower esophageal sphincter23, in particularly cephalad or superiorly to the sphincters 23. Tighterapposition is a result of the tightening and, hence, shortening of themucosa 28 along the longitudinal axis of esophagus 22. In addition, dueto the structure and orientation of the implants 52, downwardlongitudinal movement of mucosa 28 results in a downward and inwardrotation of superior portions or poles 53 of implants 52 relative toinferior poles 54 of implants 52 towards mucosa 28 which, in turn, drawsor pulls inwardly muscular walls 32 and 33 of esophagus 22. Together,these two effects significantly enhance the valve-like function ormechanism of implants 52 by inhibiting opening of esophagus 22 at loweresophageal sphincter 23 and creating a valve that is more competent thanone created by merely bulking the esophageal sphincter with injections.

The optional contrast agent in the implants permits the implants to bemonitored after completion of the procedure described above. Thus thestability of the implant and its configuration can be observed overtime. Further procedures can be performed to supplement previouslyformed implants. It should be appreciated that the implants of thepresent invention can be used as delivery vehicles for other materialssuch as radio-isotopes, chemotherapeutic agents, anti-inflammatoryagents and/or antibiotics.

The numerical sizes and ranges in the foregoing drawings are merelyexemplary and not intended to be limiting of the purview of theinvention. In addition, it should be appreciated that although fourspherical implants are shown in the figures, one or a plurality ofimplants of various sizes and shapes may be suitably formed andpositioned in the esophagus, in one or both of the circular andlongitudinal muscle layers or sub-mucosally. A plurality of implants mayalso be disposed in more than one plane and still be within the purviewof the present invention so long as they function together as avalve-like mechanism in the vicinity of the gastro-esophageal junctionto prevent gastro-esophageal reflux during increasing distension of thestomach and resultant shortening of the esophagus.

Although the method of the invention has been described as including theformation of a space by a saline solution injected into the wall 27prior to an injection of implant forming solution into the wall 27, itshould be appreciated that the space can be formed by other aqueous orphysiologic solutions or by a local anesthetic. Alternatively, theimplant forming solution can

be injected into wall 27 without the prior formation of a space by aninjection of saline solution or otherwise. A saline or other aqueous orphysiologic solution can optionally be introduced into such a spaceformed by the implant forming solution, that is after the introductionof the implant forming solution into the wall 27, to facilitatedispersion of the DMSO or other biocompatible solvent present in theimplant forming solution. It should be further appreciated that theinvention is broad enough to cover the introduction of an implantforming solution into wall 27 without the prior or subsequentintroduction of a saline or other aqueous solution into the wall 27.

The invention encompasses the creation of a valve or valve-likestructure or mechanism between other chambers in the gastrointestinaltract in order to increase or improve the competency of a sphincterbetween such chambers. Thus, where distension, increased pressure or achange in anatomy in a distal or second gastrointestinal chamber resultsin increased reflux into the first or proximal chamber due to apartially incompetent sphincter, such as anywhere in a lumen orpassageway of a body of a mammal, creation of the valve-like structurewill cause the mucosal layer to appose superior of the valve-likestructure thereby lessening reflux from the second chamber into thefirst chamber. The method is particularly suited to creating a valve inorder to supplement or replace a natural valve of a body. The method isalso applicable to and suitable for a single chamber extending to asphincter where the function and integrity of the chamber depends on thecompetency of the sphincter, such as the rectum, anus and the analsphincter. For example rectal incontinence can be treated with thismethod.

In another method of the present invention, one or more arcuate implantscan be formed in a wall forming a natural body passageway within a bodyfor augmenting the wall, for creating a valve-like mechanism or for anyother purpose. Such arcuate implants could, for example, be formed inthe vicinity of a sphincter such as the lower esophageal sphincter orthe anal sphincter for the purpose of augmenting the sphincter or someother purpose. As a further example, such arcuate implants can be formedto create a valve-like mechanism or structure in the vicinity of asphincter in such wall. In one specific example, one or more arcuateimplants 71 are formed in wall 27 in the vicinity of lower esophagealsphincter 23 and more specifically at any of the locations discussedabove (see FIG. 8). The implants 71 are preferably formed in one or bothof muscle layers 32 and 33 and more preferably between the muscle layers32 and 33. The arcuate implants 71 extend circumferentially around atleast a portion of the wall 27. The implants can subtend an angle ofless than 360° and more preferably less than 180°, as shown in FIG. 8,or can extend around substantially the entire esophagus so as to bering-like or a ring, as shown in FIG. 9 with respect to ring implant 72.

Implants 71 and 72 are formed in substantially the manner discussedabove and can be made from any of the materials discussed above. Whenthe implants are formed from a solution, and preferably the nonaqueoussolution comprised of a biocompatible polymer and a biocompatiblesolvent discussed above, the implant-forming solution can be introducedinto the wall in any suitable way such as by means of a needle. Theneedle is introduced into one of muscle layers 32 or 33 and theimplant-forming solution is then supplied to the needle. When it isdesired to form the implants between the muscle layers 32 and 33, theneedle can be moved or jiggled inwardly and/or outwardly during theinjection process until the solution starts extending around the wall 27and the passageway formed thereby to form an arcuate implant. Thejiggling of the needle enhances dissection of the muscle layers 32 and33 and facilitates introduction of the solution between these musclelayers. Once the muscle layers have been so dissected andimplant-forming solution continued to be introduced, the solution has atendency to extend around the wall as opposed to longitudinally up ordown the wall 27. A ring implant can be continuous or have ends whichabut, as in FIG. 9 with respect to implant 72. The injection needle isthus typically at the beginning or end of the arcuate implant.

The implants 71 and 72 can serve to augment or bulk wall 27 in thevicinity of lower esophageal sphincter 23, as discussed in U.S. Pat. No.6,251,063, and/or can serve to form a valve-like mechanism in the mannerdiscussed above. Ring implant 72 can further serve as a Angelchik-typeprosthesis that is internal of wall 27 for inhibiting reflux fromstomach 24.

Other suitable materials can be utilized for implant formation in themethod of the present invention. Such materials include suitablesuspensions such as injectable bioglass of the type described in Walkeret al., “Injectable Bioglass as a Potential Substitute for InjectablePolytetrafluorethylene Particles”, J. Urol., 148:645-7, 1992, smallparticle species such as polytetrafluoroethylene (PTFE) particles inglycerine such as Polytef®, biocompatible compositions comprisingdiscrete, polymeric and silicone rubber bodies such as described in U.S.Pat. Nos. 5,007,940, 5,158,573 and 5,116,387 to Berg and biocompatiblecompositions comprising carbon coated beads such as disclosed in U.S.Pat. No. 5,451,406 to Lawin. Such suitable materials for formingimplants further include collagen and other biodegradable material ofthe type disclosed in U.S. Pat. No. 4,803,075 to Wallace et al. andother known injectable materials.

From the foregoing it can be seen that a method for creating avalve-like mechanism in a natural body passageway has been provided. Insuch method, at least one implant is formed in the wall forming thenatural body passageway and such at least one implant can include aplurality of circumferentially disposed implants. The one or moreimplants can include an arcuate implant extending circumferentiallyaround at least a portion of the natural body passageway. The arcuateimplant can be a ring-like implant. The method of the invention can beutilized to enhance the lower esophageal sphincter. More specifically,the formation of valve-like implants in the esophageal wall in thevicinity of the lower esophageal sphincter enhances the competency ofthe lower esophageal sphincter helping to prevent gastroesophagealreflux.

1. A method for creating an implant in a wall forming a rectal cavity ina mammalian body and having a muscle layer extending circumferentiallyaround the rectal cavity for treating rectal incontinence comprisingintroducing a solution into the wall and forming a nonbiodegradablesolid from the solution that extends along the muscle layer to form animplant in the wall.
 2. The method of claim 1 wherein the implant isring-shaped.
 3. The method of claim 1 wherein the implant is arcuate inshape.
 4. The method of claim 1 wherein the introducing step includesprecipitating an implant from the solution.
 5. The method of claim 1further comprising a contrast agent in the solution for facilitatingvisualization of the implant in the wall.
 6. The method of claim 4wherein the contrast agent is suspended in the solution.
 7. A method forincreasing the competency of an anal sphincter in a gastrointestinaltract having a chamber extending to the anal sphincter to treat rectalincontinence, the chamber having a pressure therein and being defined bya wall having a muscle layer and a mucosal layer, comprising introducinga solution into the muscle layer in the vicinity of the anal sphincterand forming from the solution an implant in the muscle layer so as tocreate a valve-like mechanism in the wall, an increase of the pressurein the chamber causing the mucosal layer to appose in the vicinity ofthe valve-like mechanism so as to lessen the incompetence of the analsphincter.
 8. The method of claim 7 wherein the solution includes abiocompatible polymer and a biocompatible solvent.
 9. The method ofclaim 8 wherein the solution includes a contrast agent.
 10. The methodof claim 8 wherein the solution of the biocompatible polymer and thebiocompatible solvent has a composition comprising from about 2.5 toabout 8.0 weight percent of a biocompatible polymer, from about 10 toabout 40 weight percent of a water insoluble biocompatible contrastagent and from about 52 to about 87.5 weight percent of a biocompatiblesolvent.
 11. The method of claim 9 wherein the solution includes aprepolymer and wherein the forming step includes polymerizing theprepolymer in situ to form an implant in the wall.
 12. The method ofclaim 7 wherein the forming step includes precipitating an implant fromthe solution.
 13. A method for increasing the competency of an analsphincter in a gastrointestinal tract having a chamber extending to theanal sphincter to treat rectal incontinence, the chamber having apressure therein and being defined by a wall having a mucosal layer,comprising introducing a biocompatible prepolymer that is part of acomposition having a biocompatible solvent into the wall in the vicinityof the anal sphincter and polymerizing the biocompatible prepolymer insitu to form an implant in the wall so as to create a valve-likemechanism in the wall, an increase of the pressure in the chambercausing the mucosal layer to appose in the vicinity of the valve-likemechanism so as to lessen the incompetence of the anal sphincter. 14.The method of claim 13 wherein the wall has a muscle layer and whereinthe introducing step includes introducing the biocompatible prepolymerinto the muscle layer of the wall.
 15. The method of claim 13 whereinthe introducing step includes introducing the biocompatible prepolymerinto the wall beneath the mucosal layer.
 16. The method of claim 13wherein the wall has a submucosal layer and wherein the introducing stepincludes introducing the biocompatible prepolymer into the wall beneaththe submucosal layer.
 17. The method of claim 13 wherein thebiocompatible prepolymer is part of a composition having a contrastagent for facilitating visualization of the implant in the wall.
 18. Themethod of claim 13 wherein the introducing step includes extending aneedle from the gastrointestinal tract into the wall and supplying thebiocompatible prepolymer through the needle into the wall.
 19. A methodfor creating an implant in a wall having circular and longitudinalmuscle layers and forming a rectal cavity in a mammalian body to treatrectal incontinence comprising the step of introducing a solutionbetween the circular and longitudinal muscle layers so that the solutionforms an implant between the circular and longitudinal muscle layers.20. The method of claim 19 wherein the implant is ring-shaped.
 21. Themethod of claim 19 wherein the introducing step includes the step ofinjecting the solution between the circular and longitudinal musclelayers whereby at least one implant is formed from the solution.
 22. Themethod of claim 21 wherein the injecting step includes the step ofpushing a needle into one of the circular and longitudinal muscle layersand moving the needle from one of the circular and longitudinal musclelayers to the other of the circular and longitudinal muscle layerswhereby as the needle passes between the circular and longitudinalmuscle layers the solution commences flowing between the muscle layersto form the implant.
 23. The method of claim 19 wherein the solutionincludes at least one nonaqueous solution.
 24. The method of claim 23wherein the at least one nonaqueous solution is a solution of abiocompatible polymer and a biocompatible solvent.
 25. The method ofclaim 19 wherein the implant is arcuate in shape.
 26. A method forcreating an implant in a wall forming a rectal cavity in a mammalianbody and having a nonmuscular layer and a muscular layer with a borderadjoining the nonmuscular layer and the wall extending circumferentiallyaround the cavity to treat rectal incontinence comprising the steps ofintroducing a solution into the wall between the nonmuscular layer andthe muscular layer so that the solution extends along the border of themuscular layer to form an implant in the wall.
 27. The method of claim26 wherein the solution is at least one nonaqueous solution.
 28. Themethod of claim 27 wherein the at least one nonaqueous solution is asolution of a biocompatible polymer and a biocompatible solvent.
 29. Themethod of claim 26 wherein the cavity is the gastrointestinal tract. 30.A method for increasing the competency of an anal sphincter in agastrointestinal tract having a chamber extending to the anal sphincterto treat rectal incontinence, the chamber having a pressure therein andbeing defined by a wall having a muscle layer and a mucosal layer,comprising the steps of introducing at least one nonaqueous solutioninto the muscle layer in the vicinity of the anal sphincter and formingfrom the at least one nonaqueous solution an implant in the muscle layerso as to create a valve-like mechanism in the wall, an increase of thepressure in the chamber causing the mucosal layer to appose in thevicinity of the valve-like mechanism so as to lessen the incompetence ofthe anal sphincter.
 31. The method of claim 30 wherein the creating stepincludes the step of forming at least one implant in the wall.
 32. Amethod for creating an arcuate implant in a wall having circular andlongitudinal muscle layers and forming a rectal cavity in a mammalianbody to treat rectal incontinence comprising the steps of injecting asolution between the circular and longitudinal muscle layers so that thesolution extends around at least a portion of the wall to form anarcuate implant.
 33. The method of claim 32 wherein the arcuate implantis ring-shaped.
 34. The method of claim 32 wherein the injecting stepincludes the step of pushing a needle into the circular and longitudinalmuscle layers and moving the needle from one of the circular andlongitudinal muscle layers to the other of the circular and longitudinalmuscle layers whereby as the needle passes between the circular andlongitudinal muscle layers the solution commences flowing between thecircular and longitudinal muscle layers to form the arcuate implant. 35.A method for creating an arcuate implant in a wall forming a rectalcavity in a mammalian body and having a muscle layer extendingcircumferentially around the rectal cavity to treat rectal incontinencecomprising the steps of introducing a solution into the wall so that thesolution extends along the muscle layer around at least a portion of thewall to form an arcuate implant in the wall.
 36. The method of claim 35wherein the arcuate implant is ring-shaped.
 37. The method of claim 35wherein the introducing step includes the step of injecting the solutioninto the wall whereby at least one arcuate implant is formed from thesolution.